Research Progress on the Pathogenesis of Primary Enuresis in Children

Nocturnal enuresis(NE)is a common disease in children,commonly known as bedwetting.The International Children's Continence Society(ICCS)defines intermittent urinary incontinence during nighttime sleep in children aged 5 and above as enuresis.Enuresis can be divided into two types:primary nocturnal enuresis(PNE)and secondary nocturnal enuresis(SNE).PNE refers to nocturnal urinary control ability that has never been achieved for more than 6 months in children aged 5 and above with enuresis;SNE refers to the recurrence of enuresis symptoms after a period of more than 6 months of continuous nocturnal urinary control ability.SNE is relatively rare in clinical practice and is often caused by sudden stress events or other diseases such as snoring.Its pathogenesis and treatment are different from PNE.PNE is a multifactorial disease related to genetics,and its pathogenesis is not fully understood.There are not many research and review articles on its pathogenesis.In recent years,there has been significant progress in the epidemiology and pathogenesis of PNE.The following is a summary.

Phallic rubber band application to prevent enuresis unusual cause of urethral stricture in a child:A case report

BACKGROUND Urethral stricture is the abnormal narrowing of the urethra due to spongiofibrosis.The established aetiological factors for urethral stricture abound in our environment.However,the application of a penile rubber band to prevent enuresis thereby causing this pathology is not a familiar occurrence.Patients with enuresis can suffer psycho-social challenges and trauma,especially for a child due to peer stigmatization.This has a great impact on the child's psyche and may affect even his performance at school.The aim of this paper is to highlight the psychosocial impact and management challenges of a child with enuresis(nocturnal urinary incontinence).CASE SUMMARY This is the case of a 10-year-old boy who presented with a history of nocturnal urinary incontinence since birth and lower urinary tract symptoms(LUTS)for 3 years culminating in chronic urinary retention.He maintained a normal urge to micturate and continent of urine during the daytime before the onset of LUTS.He had an antecedent longstanding history of tying a rubber band to the penile shaft mostly before going to the bed at night to prevent enuresis due to his peer stigmatization.He was acutely ill-looking,with distended suprapubic region.The phallus and scrotum were enlarged and oedematous with a circumferential proximal penile shaft scar and ventral penile shaft urethrocutaneous fistula.He was diagnosed to have complete short segment bulbopenile stricture and right ectopic ureter.He subsequent had augmented anastomotic urethroplasty and bilateral non-refluxing ureteroneocystostomy at different sitting.CONCLUSION The adherence to surgical principles of urethral stricture and enuresis management where surgically correctable in a child is associated with the resolution of enuresis and social reintegration.

Management of nocturnal enuresis-myths and facts

Nocturnal enuresis often causes considerable distress or functional impairment to patient and their parents necessitating a multidisciplinary approach from paediatrician, paediatric nephrologist, urologists and psychiatrist. Mechanisms of monosymptomatic nocturnal enuresis are mainly nocturnal polyuria, bladder overactivity and failure to awaken from sleep in response to bladder sensations. Goal oriented and etiology wise treatment includes simple behavioral intervention, conditioning alarm regimen and pharmacotherapy with desmopressin, imipramine and anticholinergic drugs. Symptoms often recurs requiring change over or combination of different modes of treatment.

The post-treatment effects of enterobiasis on the occurrence of enuresis among children in Calabar,Nigeria

Objective:To investigate the relationship between enterobiasis and enuresis before and after albendazole therapy among 632 children,aged,5-14 years,in Calabar,Nigeria.Methods:The scotch tape(cellotape) technique was used for the detection of eggs of Enterobius vermicularis (E.vermicularis) while questionnaire-based interviews were used for screening for anal itching and/or enuresis among study participants.All subjects found positive for Enterobius infection as confirmed by the presence of eggs and those with persistent anal itching(both enuretic and nonenuretic) were treated with 400 mg of albendazole given as a single dose.The treated subjects were re-assessed post-treatment to ascertain whether they were cured and also to determine their enuretic status(for the entireties).Results:The overall prevalences of Enterobius infection, anal itching,and enuresis prior to albendazole therapy were 6.8%,42.9%,and 35.6%respectively. There was no statistically significant difference in the prevalence of these parameters by the socio-economic class of subjects(P = 0.462,P - 0.647,and P = 0.610,respectively).The pretreatment prevalences of enuresis among Enterobius and anal itching-positive subjects were 53.5%and 49.8%,respectively versus 34.3%and 24.9%,respectively among their negative counterpart(P = 0.012 and P 【 0.001,respectively).Four(20%) out of the 20 enuretic children found Enterobius egg-negative after albendazole therapy were equally cured while 8(40%) had reduction of their enuresis,thus giving a total resolution rate of 60%.Similarly,64.2%resolution (25%cure and 32.8%reduction) of enuresis was observed amongst 120 anal itching-cured/ enuretic children.Enuretic status of the Enterobius-lanal itching-uncured subjects,on the other hand,remained unchanged post-treatment.Conclusions:This study is suggestive of the involvement of E.vermicularis in the aetiology of enuresis in Calabar.Children presenting with, especially,uncomplicated enuresis should be screened for enterobiasis.

CLINICAL OBSERVATION ON 68 CASES OF ENURESIS TREATED BY MOXIBUSTION COMBINED WITH FINGER-MASSAGE METHOD

The therapeutic effect of moxibustion combined with finger-massage method was observed in 68 patients suffering from enuresis. The results showed that (1) The present therapy is effective for enuresis with cure rate of 66.18% and total effective rate of 92. 65 %; (2) The curative effects was related with the syndrome differentiation (P <0. 01), e. g. it is effective for deficiency of kidney-Yang and deficiency of Qi in lung and spleen types, but ineffective for the type of downward flow of damp-heat; (3) The therapeutic effect was also closely related with the course of disease. The shorter the course of illness lasted, the more effective the therapy was, indicating that such patients should be treated in the early stage. This method is not only comparable to other conventional acupuncture methods in respects of the cure rate and total effective rate, but is also simple to apply, safe to use, easy to be accepted by children and adverse-effect free. It is deserved to be popularized as a effective therapy for enuresis in children patients.

Acupuncture Treatment of Enuresis

Case HistoryYang××,a male middle school student aged16 years,paid his first visit on March 5,1990,withthe chief complaint of bed-wetting for more than tenyears.The patient had got this problem since hischildhood.In better conditions,the bed-wettingoccurred once in several nights;while in worseconditions,it might happen several times a night.Heused to sleep so soundly that was difficult to wakehim up.The condition would tend to become

CLINICAL OBSERVATION ON 32 CASES OF FUNCTIONAL ENURESIS TREATED WITH ACUPUNCTURE AT BAIHUI(GV 20)

Acupuncture at Baihui（GV 20）was employed in treating 32 cases of functionalenuresis.As a result,the curative rate reached 81.25％,but that in control group of 32 cases withoutneedling Baihui point was 56.25％.There was a significant difference in statistics（P【0.05）.It indi- cates that Baihui can enhance the therapeutic effect of acupuncture on treating enuresis.

Mechanism of Xingshen Zhiyi prescription in the treatment of enuresis based on network pharmacology

Objective:To explore the mechanism of Xingshen Zhiyi Recipe(XSZYF)in the treatment of Nocturnal Enuresis(NE)based on network pharmacology.Methods:TCMSP,DrugBank databases,PubMed and CNKI were used to obtain the active ingredients and corresponding targets of XSZYF.NE targets were obtained from GeneCard and OMIM databases.Cytoscape software was used to construct a drug-disease-target network model.The analysis was performed.The protein interaction network(PPI)was constructed using the STRING database.The gene ontology functional annotation(GO)and the Tokyo Genomic Encyclopedia(KEGG)pathway enrichment analysis were performed on key targets using the DAVID online tool.Surflex docking software was used for the analysis.Docking of key active ingredients and key targets to verify the results of network analysis.Results:199 gene targets of XSZYF were obtained,and 2486 gene targets of NE.Network analysis results showed that the key targets of XSZYF for treating NE include CHRM3,CHRM2,ADRB3,etc.Involved in regulating neuroactive ligand-receptor interactions,calcium signaling pathways,etc.Conclusion:This study revealed the material basis and action mechanism of XSZYF in treating NE from the perspective of network pharmacology.

No Correlation between <i>AVPR</i>1A Promoter Polymorphisms and Prepulse Inhibition in Patients with Nocturnal Enuresis

Introduction: A correlation between AVPR1A promoter polymorphisms and prepulse inhibition (PPI) of startle reflexes has been described in healthy adults. Many children with nocturnal enuresis (NE) have a reduced PPI and treatment with desamino arginine vasopressin (dDAVP), a ligand of the arginine vasopressin receptor 1A (AVPR1A), and both improve clanical symptoms and significantly increase PPI. Methods: In 17 children (median 9.1 years, range 6.4-17.3) with NE, promoter repeats within the RS1 and RS3 regions of AVPR1A were quantified and correlated to PPI (native and age-adjusted). Results: No direct correlation was found between the number of promoter repeats at RS1 and PPI (correlation coefficient—0.240, p = 0.346) or RS3 and PPI (correlation coefficient—0.0192, p = 0.936), with no change through age-adjustment of PPI. The different RS3 length subgroups did not show differences in PPI, nor did differentiation of NE according to clinical subtype or treatment response to dDAVP show differences in the number of promoter repeats. Conclusion: The missing reproducibility of the correlation between AVPR1A promoter polymorphisms and PPI in a group with wide range of PPI suggests a more complex interaction. Therefore, further investigations are needed to analyze this very plausible interaction. Conditions with a reduced PPI, such as enuresis, schizophrenia or autism, are particularly interesting for this research.

Enuresis and sleep disordered breathing:An old and new link

The causes of nocturnal enuresis(NE) are likely multifactorial.It has been related to several(urologicalnephrological-hormonal) reasons but clear and univocal pathogenesis remains mostly undetermined.Sleep disordered breathing(SDB) is a syndrome of upper airway dysfunction that occurs during sleep and is characterized by snoring and/or increased respiratory effort secondary to increased upper airway resistance and pharyngeal collapsibility.Adenotonsillar hypertrophy is the main cause of SDB in children.To date,several studies have associated childhood NE with coexistent SDB.Adenotonsillectomy was successful for both SDB and NE in about half of patients.Unfortunately,practical consensus guidelines for the management of primary NE do not mention,or marginally concern,SDB in these children,particularly in those who have treatment resistance and comorbidities.The concerns regard the concomitant presence of two relatively frequent sleep disorders,raising the question whether they are really coincidental problems of childhood.

Professor JIA Chun-sheng's experience for pediatric enuresis

To introduce the experience of professor JIA Chun-sheng in treatment of primary and simple enuresis. Professor JIA Chun-sheng believes that most children with pediatric enuresis have the manifestation of both spleen deficiency and kidney deficiency, and it is rare that the patients have one of the two kinds of manifestation. The pathogenesis is as follows： kidney yang deficiency and depletion, steaming weakness, and caused by spleen qi deficiency qi deficiency and sinking, and the bladder failing to ensure retention results in failure of body fluids to be stored, so that enuresis is induced. On the basis of the above theory, professor JIA Chun-sheng proposed the treatment rules of ＂nourishing earth and banking up original qi, opening the orifices and awakening the spirit＂, and selected Bǎihuì（百会 GV 20）, Qìhǎi（气海 CV 6）, Guānyuán（关元 CV 4）, Zúsānlǐ（足三里 ST 36）, Sānyīnjiāo（三阴交 SP 6） and Tàixī（太溪 KI 3） as the basic acupoints. Corresponding acupoints were increased or reduced according to different patterns, and good efficacy has been obtained.

Better outcomes with desmopressin melt than enuretic alarm therapy in children with nocturnal enuresis during coronavirus disease 2019(COVID-19)

Objectives:This study aimed to investigate the effect of the coronavirus disease 2019(COVID-19)pandemic on the treatment of children with primary monosymptomatic nocturnal enuresis(MNE)with desmopressin melt versus an enuresis alarm.Materials and methods:This study included 56 children with primary MNE who were taking desmopressin melt or using an alarm.Their anxiety levels were evaluated using the Social Anxiety Scale for Children-Revised.For both treatment methods,data from a 3-month bedwetting diary between the third and sixth months of the pre-pandemic treatment were compared with those assessed during the same period during the pandemic.Results:Prior to the COVID-19 pandemic,the median 3-month mean frequency of MNE was 1(0-7.67)in children using desmopressin melt versus 1.33(0-6)in those using alarm treatment(p=0.095).During the COVID-19 pandemic period,the median monthly mean frequency of MNE was 1.33(0-7.33)in children using desmopressin melt versus 6(1.33-13)in those using alarm treatment(p<0.001).Conclusions:The COVID-19 pandemic and its accompanying psychological effects did not affect the treatment efficacy of desmopressin melt in children with primary MNE but did adversely affect that of enuresis alarms.

Case of geriatric enuresis

Professor JI O.ing-shan＇s experiences in treating geriatric enuresis were introduced, Professor JI Qing-shan emphasizes the pathogenesis, and acupoint selection was precise and appropriate, values needling sensation, and emphasize reinforcing and reducing method, combine acupuncture and moxibustion which can warm and unblock meridians. Acupuncture at Sanyinjiao （三阴交SP 6）, enuresis point, Guanyuan （关元 CV 4） and Qihai （气海 CV 6） was conducted. The needle was inserted into enuresis point for 2.5 mm, twirling for reducing was conducted to the extent that the needling sensation delivered to abdomen; twirling for reinforcing was conducted at CV 4 and CV 6 to the extent that the needling sensation radiated to pudendum. Reinforcing method was conducted at SP 6. The patient＇s family members were advised to conduct moxa stick moxibustion at CV 6, CV 4 and Shenshu （肾俞BL 23） for therapeutic effect consolidation, good efficacy was obtained.

Current perspectives on the correlation of nocturnal enuresis with obstructive sleep apnea in children

Background Obstructive sleep apnea (OSA) and nocturnal enuresis (NE) are common clinical problems in children.OSA and NE are thought to be interrelated,but the exact pathophysiological mechanisms are not yet clear.This review aims to explain the possible pathogenesis of NE in children with OSA.Date sources We have retrieved all relevant original articles from Database that have been published so far,including the prevalence studies of NE and OSA in children,sleep characteristic studies that use polysomnography (PSG) to focus on children with NE,and studies on the relationship between OSA and NE.Results Clinical studies have revealed that the risk of NE in children with OSA was increased compared with that of their healthy peers.This increased risk may be associated with sleep disorders,bladder instability,detrusor overactivity,nocturnal polyuria,endocrine and metabolic disorders,and inflammation.Conclusions Cardiopulmonary and renal reflex-induced neuroendocrine disorder may play an important role in the mechanism of NE in children with OSA,but this remains to be confirmed by animal studies.Other causes such as oxidative stress and inflammatory responses need to be further researched.

Evaluation of a new frequency-volume chart for children with primary monosymptomatic nocturnal enuresis:a prospective,comparative study

Introduction To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis(PMNE),a new modified 3-day weekend frequency-volume chart(FVC)was designed,and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society(ICCS)recommended voiding diary.Methods A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary.The primary outcome measure was the compliance,assessed by comparing the completing index and the quality score of diaries between two groups.The secondary outcome measure was the validity,evaluated by comparing the constituent of subtypes,micturition parameters and response rate to desmopressin.Results Among the 1200 participants enrolled in the study,447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary.The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group.In addition,there was no significant difference between these two groups in the subtype classification,or in the response rate to desmopressin.Conclusions The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.

Research Advance on Enuresis with Hemirachischisis Treated by Regulating Governor Vessel

The patients with primary enuresis complicating with hemirachischisis were treated by routine manipulations as well as the acupoints and manual methods to unblock and regulate Governor Vessel. Excellent effects have been obtained.

Treatment of 43 Cases of Enuresis by Acupuncture

By classification with syndrome differentiation into the three patterns of deficient cold in the lower energizer, qi deficiency in the spleen and lung and damp heat in the Liver Meridian, 43 cases of enuresis were treated by puncturing Baihui (GV 20), Guanyuan (CV 4) and Shanyinjiao (SP 6). After two courses of the treatment, the results showed cure in 28 cases, improvement in 13 cases and failure in 2 cases. Key Words Enuresis - Acupuncture Therapy - Syndrome Differ Classification Translator: HUANG Guo-qi

Urodynamic changes in a female case of obstructive sleep apnea syndrome with enuresis： 7 years＇ follow-up

Obstructive sleep apnea syndrome （OSAS） is characterized by repetitive upper airway occlusion resulting in apnea lasting 10 seconds or more. Clinical manifestations include snoring, daytime somnolence, intellectual deficiency, sexual impotence, and nocturnal polyuria. Enuresis associated with OSAS is suggested to be more common in children than in adults） In children, removal of upper airway obstruction by surgical intervention （tonsillectomy and/or adenoidectomy） leads to a significant decrease in or complete cure of enuresis. Although a great deal has been written concerning aduk enuresis,

Therapeutic Observation on Treatment of Enuresis with Combined Auricular Pressure and Tuina

Ninety-two cases of enuresis were treated with auricular point pressure onthe kidney （MA SC）, bladder （MASC 8）, lung （MAIC 1）, heart （MA IC）, liver （MASC 5）, Er Shenmen（MA-TF 1）, Zhen （MA-AT） and Subcortex （MAAT 1） plus tuina. After treatment, 61 cases were cured, 28 cases were effective and 3 cases were ineffective, with an effective rate of 96.7%.

Treatment of 36 Cases of Infantile Enuresis by Acupuncture

Treated 36 cases of infantile enuresis by acupuncturing Zuyunganqu (Foot Motor Sensory Area) Guanyuan (CV 4), Qihai (CV 6), Zhongwan (CV 12), Zusanli (ST 36), Yinlingquan (SP 9), Pishu (BL 20), Weishu (BL 21) and Shenshu (BL 23). After two courses, 29 cases were cured, 5 cases were improvement and 2cases were no effect. Key Words Enuresis - Scalp Acupuncture - Acupuncture Therapy - Child